A gene-dosage PCR method for the detection of elastin gene deletions in patients with Williams syndrome

Williams syndrome (WS) is a multisystem developmental disorder associated with microdeletions at 7q11.23 that involve several genes, including the elastin gene. Using genomic DNA from a panel of normal individuals and WS patients with established hemizygosity of the elastin gene locus, we have developed a quantitative polymerase chain reaction (PCR)-based gene-dosage assay that rapidly detects the loss of one allele of the elastin gene. Using this procedure, we also studied a family in which the proband was previously diagnosed with WS and her mother with a balanced 7q translocation [t(7:11)(q34;q13)]. Using DNA isolated from buccal smears obtained from several individuals in this family we were able to establish normal disomy at 7q in all family members except for the proband, in which we established hemizygosity at the elastin gene locus. We were also able to successfully infer normal disomy in an unborn child in this family. The rapid diagnostic procedure described here may have a variety of applications, including fine mapping of deletion breakpoints at 7q11.23 associated with WS.